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Background and purpose: Data on current cardiovascular event rates in patients with asymptomatic carotid artery stenosis (ACAS) are sparse. We compared the 1-year outcomes of patients with ACAS ≥70% versus patients without ACAS in an international, prospective cohort of outpatients with or at risk of atherothrombosis. Methods: The Reduction of Atherothrombosis for Continued Health Registry enrolled patients with either ≥3 atherothrombotic risk factors or established atherothrombotic disease. We investigated the 1-year follow-up data of patients for whom physicians reported presence/absence of ACAS at the time of inclusion. Results: Compared with patients without ACAS ( n = 30 329), patients with ACAS ( n = 3164) had higher age- and sex-adjusted 1-year rates of transient ischaemic attack (3.51% vs. 1.61%, P < 0.0001), non-fatal stroke (2.65% vs. 1.75%, P = 0.0009), fatal stroke (0.49% vs. 0.26%, P = 0.04), cardiovascular death (2.29% vs. 1.52%, P = 0.002), the composite end-point cardiovascular death/myocardial infarction/stroke (6.03% vs. 4.29%, P < 0.0001) and bleeding events (1.41% vs. 0.81%, P = 0.002). In patients with ACAS, Cox regression analyses identified history of cerebrovascular ischaemic events as most important predictor of future stroke (HR 3.21, 95% CI 1.82–5.65, P < 0.0001). Conclusion: Asymptomatic carotid artery stenosis was associated with high 1-year rates of cardiovascular and cerebrovascular ischaemic events. Stroke was powerfully predicted by prior cerebrovascular ischaemic events. [ABSTRACT FROM AUTHOR]

Context: More than 50 million US adults take aspirin regularly for long-term prevention of cardiovascular disease, typically either 81 mg/d or 325 mg/d. Controversy remains regarding the most appropriate long-term daily dose.Objective: To review the mechanism of action of aspirin and the clinical literature for relationships among aspirin dosage, efficacy, and safety.Evidence Acquisition: A systematic review of the English-language literature was undertaken using MEDLINE and EMBASE (searched through February 2007) and the search term aspirin or acetylsalicylic acid and dose. The search was limited to clinical trials and was extended by a review of bibliographies of pertinent reports of original data and review articles. Published prospective studies using different aspirin dosages in the setting of cardiovascular disease were included.Evidence Synthesis: Although pharmacodynamic data demonstrate that long-term aspirin dosages as low as 30 mg/d are adequate to fully inhibit platelet thromboxane production, dosages as high as 1300 mg/d are approved for use. In the United States, 81 mg/d of aspirin is prescribed most commonly (60%), followed by 325 mg/d (35%). The available evidence, predominantly from secondary-prevention observational studies, supports that dosages greater than 75 to 81 mg/d do not enhance efficacy, whereas larger dosages are associated with an increased incidence of bleeding events, primarily related to gastrointestinal tract toxicity.Conclusions: Currently available clinical data do not support the routine, long-term use of aspirin dosages greater than 75 to 81 mg/d in the setting of cardiovascular disease prevention. Higher dosages, which may be commonly prescribed, do not better prevent events but are associated with increased risks of gastrointestinal bleeding. [ABSTRACT FROM AUTHOR]

Objective: To confirm the overall benefit of drug eluting stents (DES), to evaluate the effect of different DES, and to assess the global safety of DES compared with bare stents through a meta-analysis of randomised controlled trials. Methods: Randomised controlled trials comparing sirolimus and derivates or paclitaxel and derivates eluting stents versus bare stents. Binary restenosis and major adverse cardiac events (MACE) were chosen as primary end points. Death, Q wave myocardial infarction (MI), and stent thrombosis up to 12 months' follow up were also analysed. Results: MACE overall occurrence was highly reduced with DES from 19.9% to 10.1% (odds ratio (OR) 0.46, 95% confidence interval (CI) 0.41 to 0.52, p < 0.001). A significant heterogeneity (p < 0.001) was found between subgroups according to the drug: MACE OR was 0.28 (95% CI 0.22 to 0.35) in the sirolimus subgroup and 0.62 (95% CI 0.53 to 0.73) in the paclitaxel subgroup. Restenosis was also highly reduced from 31.7% with bare stents to 10.5% with DES (OR 0.25, 95% CI 0.22 to 0.29, p < 0.001 ) with a similar heterogeneity between subgroups. Mortality, Q wave MI, and stent thrombosis were not significantly different between DES and control group, whereas Q wave MI and stent thrombosis tended to be more frequent with paclitaxel. Conclusion: This meta-analysis confirms the overall benefit of DES on restenosis and MACE with significant heterogeneity between drugs, suggesting higher efficacy of sirolimus eluting stents. Additional data with longer follow up and in high risk populations are needed to clarify issues on stent thrombosis. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVES: The clinical manifestations of acute coronary syndromes (ACSs) vary, and patients present frequently with symptoms other than chest pain. In this analysis, a large contemporary database has been accessed to define the frequency, clinical characteristics, and outcomes of patients presenting without chest pain across different diagnostic categories of ACS. DESIGN AND SETTING: The Global Registry of Acute Coronary Events is a multinational, prospective, observational study involving 14 countries. PATIENTS: Patients presenting to the hospital with a suspected ACS were stratified according to whether their predominant presenting symptoms included chest pain (ie, typical) or did not (ie, atypical). Demographics, medical history, hospital management, and outcomes were compared. MEASUREMENTS AND RESULTS: Of the 20,881 patients in this analysis, 1,763 (8.4%) presented without chest pain, 23.8% of whom were not initially recognized as having an ACS. They were less likely to receive effective cardiac medications, and experienced greater hospital morbidity and mortality (13% vs 4.3%, respectively; p < 0.0001) than did patients with typical symptoms. After adjusting for potentially confounding variables, increased hospital mortality rates were noted in patients with dominant presenting symptoms of presyncope/syncope (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.4 to 2.9), nausea or vomiting (OR, 1.6; 95% CI, 1.1 to 2.4), and dyspnea (OR, 1.4; 95% CI, 1.1 to 1.9), and in those with painless presentations of unstable angina (OR, 2.2; 95% CI, 1.4 to 3.5) and ST-segment elevation myocardial infarction (OR, 1.7; 95% CI, 1.2 to 2.2). CONCLUSION: Patients with ACSs who present without chest pain are frequently misdiagnosed and undertreated. With the exception of diaphoresis, each dominant presenting symptom independently identifies a population that is at increased risk of dying. These patients experience greater morbidity and a higher mortality across the spectrum of ACSs. [ABSTRACT FROM AUTHOR]

The low-molecular-weight heparins (LMWHs) enoxaparin and dalteparin have shown superior and equivalent efficacy, respectively, over unfractionated heparin (UFH) in patients with unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI). This study aimed to identify markers of blood cell activation that are independent predictors of outcomes at 1 month and to compare the effects of enoxaparin, dalteparin, and UFH on any such markers. In this multicenter, prospective, open-label study, 141 patients with UAP or NSTEMI were randomized to treatment for 48 to 120 hours with enoxaparin (n = 46), dalteparin (n = 48), or UFH (n = 47). Blood samples were taken at the time of randomization and after > or =48 hours of treatment but before catheterization. Multivariate analysis identified increased plasma levels of von Willebrand factor (vWF) and decreased platelet levels of glycoprotein Ib/IX complexes as independent predictors of 1-month adverse outcome (a composite of death, myocardial infarction, and recurrent ischemia). vWF release was strongly related to and may have been released by inflammation as measured by C-reactive protein. Both LMWHs reduced the release of vWF in plasma (as well as C-reactive protein) compared with UFH. Enoxaparin had a more favorable effect on glycoprotein Ib/IX complexes than either dalteparin or UFH. The incidence of the composite clinical efficacy end point was: 13% (enoxaparin), 19% (dalteparin), and 28% (UFH). vWF and its receptor glycoprotein Ib/IX play a key role in acute coronary syndromes. vWF is linked to inflammation and, like glycoprotein Ib/IX, is affected more favorably by the LWMHs than by UFH. [ABSTRACT FROM AUTHOR]

Aims There have been no large observational studies attempting to identify predictors of major bleeding in patients with acute coronary syndromes (ACS), particularly from a multinational perspective. The objective of our study was thus to develop a prediction rule for the identification of patients with ACS at higher risk of major bleeding.Methods and results Data from 24 045 patients from the Global Registry of Acute Coronary Events (GRACE) were analysed. Factors associated with major bleeding were identified using logistic regression analysis. Predictive models were developed for the overall patient population and for subgroups of patients with ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina. The overall incidence of major bleeding was 3.9% (4.8% in patients with STEMI, 4.7% in patients with NSTEMI and 2.3% in patients with unstable angina). Advanced age, female sex, history of bleeding, and renal insufficiency were independently associated with a higher risk of bleeding (P<0.01). The association remained after adjustment for hospital therapies and performance of invasive procedures. After adjustment for a variety of potential confounders, major bleeding was significantly associated with an increased risk of hospital death (adjusted odds ratio 1.64, 95% confidence interval 1.18, 2.28).Conclusions In routine clinical practice, major bleeding is a relatively frequent non-cardiac complication of contemporary therapy for ACS and it is associated with a poor hospital prognosis. Simple baseline demographic and clinical characteristics identify patients at increased risk of major bleeding. [ABSTRACT FROM PUBLISHER]

Objectives: In the present study, we describe the characteristics and examine the anticoagulation levels and safety of subcutaneous enoxaparin in unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI) patients who would not have been eligible in the Efficacy Safety Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) and Thrombolysis In Myocardial Infarction (TIMI)-11B trials.Background: It is not known whether the benefit shown with enoxaparin in the selected population of pivotal trials can be extended to the real world.Methods: In our center, all patients with UA/NSTEMI are anticoagulated with subcutaneous enoxaparin adjusted to creatinine clearance. Among 515 consecutive patients, we identified 174 who would not have been eligible for ESSENCE or TIMI-11B ("EP" group for excluded patients). We evaluated cardiovascular death or non-fatal myocardial infarction (MI), as well as major and minor bleeding events, at 30 days in the EP group and in patients without any of the exclusion criteria ("NEP" group for non-excluded patients).Results: This EP group was older, had a higher female/male ratio, and more frequently had a history of MI or a diagnosis of non-Q MI on admission than the NEP group. The distribution of the anti-Xa activity was similar in both groups. The bleeding rates (major and minor) at 30 days were similar in the EP and NEP groups (2.3% vs. 2.9%, respectively, P = NS). On multivariate analysis, the use of glycoprotein IIb/IIIa inhibitors and the presence of hypertension were the only independent predictors of bleeding found in the whole population. Compared with the NEP group, the EP group had a fourfold increased rate of death or MI at 30 days (15.5% vs. 4.1%, p < 0.01). On multivariate analysis, the independent predictors of death or MI at 30 days were NSTEMI on admission, creatinine clearance, and heart failure.Conclusions: Patients who do not fit the enrollment criteria of ESSENCE/TIMI-11B have higher risk baseline characteristics for both bleeding and ischemic events. In these patients, enoxaparin with dose adjustment to creatinine clearance provides adequate anti-Xa levels and no excess of bleeding. [ABSTRACT FROM AUTHOR]

Objectives: To perform an evaluation from the societal perspective of the cost of treatment with enoxaparin sodium versus unfractionated heparin (UFH) in patients with unstable angina and non-Q wave myocardial infarction in France.Design: Four complementary cost-minimisation analyses based on the results of the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events (ESSENCE) international trial were conducted. We assessed differences in medical resource consumption and in duration of hospital stay in the whole study population (n = 3171) and for the French patients (n = 133).Results: Results were consistent for the study group as a whole and for the French subgroup. Among patients treated with enoxaparin sodium, there was a statistically significant reduction in the use of angiography and percutaneous transluminal coronary angioplasty (whole group study: p = 0.024 and 0.006, respectively) and a trend towards shorter lengths of hospital stay. The differences in angiography and angioplasty rates led to estimated average net cost savings with enoxaparin sodium of French Francs (FF)1555 per treated patient (whole study population) and FF9993 (French subgroup) [1996 values]. The analyses based on the duration of hospital stay resulted in estimated net cost savings with enoxaparin sodium of between FF1014 per treated patient (whole study population) and FF2804 (French subgroup).Conclusion: Our study confirmed earlier results which show that enoxaparin sodium is cost saving in the treatment of unstable angina. [ABSTRACT FROM AUTHOR]

Sickle cell disease is the most frequent genetic hemoglobinopathy worldwide and early childhood mortality has dramatically decreased in high-income countries. However, in the aging sickle cell disease population, the morbidity related to chronic organ damage, especially kidney and heart, has become a major concern. The disease is well characterized in homozygous SS patients, but the complications associated with Haemoglobin SC disease (HbSC) are mostly unknown. Dyspnea is frequent in SS patients and associated with poor quality of life, this symptom was not investigated in HbSC patients. Our objective is to investigate the prevalence and the factors associated with dyspnea in HbSC patients. A total of 221 HbSC patients (mean age 35 years, 47% men) were prospectively investigated. Clinical and biological data were collected, and 109 (49%) patients underwent an echocardiography. A dyspnea was observed in 28 (13%) patients. Compared to the rest of the cohort, these patients were older and had a lower hemoglobin level (P < 0,001). In the subgroup with echocardiographic examination, the left ventricular (LV) ejection fraction was preserved in all the patients. An LV diastolic dysfunction was diagnosed in 25 (23%) patients, 10 had dyspnea and 15 were asymptomatic (P = 0.06). In multivariable analysis, age (Odds ratio 0,94 [0,91–0,97]) and hemoglobin level (1,74 [1,17–2,58]) were independently associated with dyspnea (Fig. 1). Dyspnea is relatively uncommon in adult HbSC patients and related to age and hemoglobin level. Cardiac involvement seems not to be a major factor associated to dyspnea in HbSC patients. [ABSTRACT FROM AUTHOR]

Surgical treatment is required in approximately half of the patients with infective endocarditis (IE) because of severe complications. To date there is no recommendation favoring a specific valve substitute for IE treatment and accordingly there is a wide variation in routine surgical management of these patients. The purpose of this study is to describe surgical practices in our center and to investigate the impact on clinical outcomes. All patients with native valve left-sided IE, who underwent valve replacement surgery with a mechanical or biological prosthesis in our institution between 1 January 2006 and 31 December 2018 were enrolled in this retrospective study. A total of 303 patients were included (mean age = 58 years, 80% men). Patients in whom a biological valve was chosen (64%, n = 194) were older and had more comorbid conditions compared to patients who received a mechanical valve (36%, n = 109). In hospital mortality was respectively 19% (n = 36) in the bioprosthesis group avec 3% (n = 3) in the mechanical valve group (P < 0.0001). The mortality rates at 1 and 3 years were 35% and 41% in the biological valve group, these rates were 8% and 15% in the mechanical valve group. Factors associated to in hospital and mid term mortality were age, comorbid conditions, hemodynamic failure, a double valve replacement or associated bypass surgery. The type of the implanted valve substitute was not independently associated with mortality. For surgical management of IE, a biological valve is the most used valve substitute in our institution. Mechanical valves seem to be implanted in a very selected and low-risk patient subgroup. The valve substitute does not appear to be related to in hospital nor to midterm mortality rates. [ABSTRACT FROM AUTHOR]

Coronary blood flow reserve may be affected by several physiological variables besides hydraulic impediment to flow. A hyperaemic response induced by hyperosmolar radiopaque contrast medium was recorded in the left anterior descending and left circumflex arteries with a steerable pulsed Doppler system in four patients with Q wave anterior myocardial infarction chronic scar and non-stenotic coronary arteries. Resting flow velocities were similar in both arteries. The magnitude of the hyperaemic response induced by contrast media in the circumflex artery (mean flow velocity increase from 5.9±2.5 baseline to 12.2 ±0.6 cm s at peak flow, P<0.05) was almost twice that induced in the left anterior descending artery (mean flow velocity increase from 6.1±2.2 baseline to 7.4±2.6cms1 at peak flow, P = N.S.). The peak flow to baseline flow velocities ratios were 1.22 ±0.15 in the left anterior descending artery vs 2.23 ±0.75 in the circumflex artery. Thus when a post-myocardial infarction chronic scar is supplied by a non-stenotic coronary artery, the coronary blood flow hyperaemic response to contrast media-induced transient ischaemia is decreased, suggesting that coronary blood flow reserve depends on a myocardial metabolic stimulus which is impaired by ischaemic cell death. [ABSTRACT FROM PUBLISHER]

Introduction Serum cholesterol efflux capacity, a biomarker of the early step of the reverse cholesterol transport, has been associated with atherosclerosis independently of high-density lipoprotein (HDL) cholesterol level. Objective To evaluate the prognostic impact of serum cholesterol efflux capacity on mortality in a large cohort of patients hospitalized for an acute myocardial infarction (MI). Method Serum cholesterol efflux capacity was measured in 1,609 consecutive patients admitted with an acute MI. Results In a fully adjusted model that included age, sex, traditional cardiovascular risk factors including lipid levels, and prognostic factors of MI, serum cholesterol efflux capacity was a strong predictor of survival (adjusted hazard ratio for mortality per 1-SD increase in serum cholesterol efflux capacity, 0.79; 95% confidence interval: 0.66 to 0.95; P = 0.0132). Patients displaying an elevated serum cholesterol efflux capacity had a marked lower rate of mortality at 6 years (adjusted hazard ratio: 0.54 [0.32 to 0.89]; P = 0.0165) as compared with patients with reduced serum cholesterol efflux capacity. Conclusion Serum cholesterol efflux capacity, an integrative marker of reverse cholesterol transport pathway and efficacy, was inversely associated with all-cause mortality in MI patients independently of HDL cholesterol level and other risk factors. [ABSTRACT FROM AUTHOR]

Percutaneous left atrial appendage (LAA) closure is increasingly used to prevent strokes in patients with atrial fibrillation (AF). The alteration of left atrial (LA) compliance by LAA occlusion may represent a clinical issue in AF patients, which are also at high risk of heart failure (HF). To describe the impact of LAA occlusion on LA hemodynamics. This study included patients who underwent LAA occlusion procedure in whom LA pressure curves were recorded, before and immediately after device implantation. Mean LA pressure was defined as abnormal when > 15 mmHg. We recorded all cause death and hospitalizations for congestive HF at longest follow-up. We enrolled 86 patients (78 ± 8 years, 46 men). The mean LA pressure increased significatively after LAA closure from 12.6 ± 3.9 mmHg to 15.6 ± 5.2 mmHg (P < 0.0001, Fig. 1). The prevalence of abnormal mean LA pressure was 20% at baseline and 45% after LAA closure (P = 0.006). Post procedural LA pressure elevation was not related to procedure duration nor to fluid expansion volume. After an average follow-up of 363 [120–731] days, 9 (10%) patients died and 6 (7%) were hospitalized for HF. There were more events (N = 11 of 39, 28%) in patients with abnormal post procedural LA pressure as compared to the rest of the population (N = 4 of 47, 9%; P = 0.02). All HF hospitalizations occurred in patients with abnormal post procedural LA pressure (P = 0.0007). Catheter-based LAA occlusion induces an acute alteration of LA hemodynamics that seems to be linked to HF episodes. Further studies are warranted to investigate HF as a potential late complication of LAA closure. [ABSTRACT FROM AUTHOR]

The optimal management of left ventricular thrombus (LVT) is unknown, particularly with the emergence of the non-vitamin K antagonist anticoagulants (NOACs). To identify the independent correlates of LVT regression and clinical outcomes. A computerized case sensitive search on 90 065 consecutive echocardiograms performed between January 2011 and December 2017 identified patients with a LVT. Repeated echocardiographic data, treatment and major adverse cardiac events (MACE), including death, stroke, myocardial infarction or acute peripheral artery emboli were analyzed as well as major bleeding events (BARC ≥ 3) and all-cause mortality. We included 159 patients with an LVT confirmed by two independent experts. Patients were treated by vitamin K antagonists (48.4%), parenteral heparins (27.7%) and NOACs (22.6%) with additional antiplatelet therapy in 67.9% of the population. Total LVT regression was reached in 62.3% of the patients in a median time of 103 [32–392] days. The independent correlates associated with LVT regression were a non-ischemic cardiomyopathy (HR 0.36; 95%CI [0.19–0.69], P = 0.002) and a smaller baseline thrombus area (HR 0.66; 95%CI [0.45–0.96], P = 0.031). Cardiovascular events were frequent with 37.1% of MACE, 18.9% of major bleeding and 13.2% of all-cause mortality during a median follow-up of 632 [187–1126] days. A left ventricular ejection fraction >35% (HR 0.46; 95%CI [0.23–0.93], P = 0.029) and an anticoagulation therapy > 3 months (HR 0.42; 95%CI [0.20–0.88], P = 0.021) were independently associated with less MACE. A reduced risk of mortality was observed among patients that obtained a total LVT regression (HR 0.48; 95%CI [0.23–0.98]; P = 0.039) (Fig. 1). The presence of LVT was associated with a very high risk of MACE and mortality. Total thrombus regression, obtained with either vitamin K antagonists or NOACs, led to a better prognosis. [ABSTRACT FROM AUTHOR]

Reports on the conclusion of randomised trials that percutaneous coronary intervention is the best reperfusion for patients with acute myocardial infarction. Limits of application to routine practice; Comparison of therapy against thrombolysis with modern agents; Publication of cardiovascular patient outcomes.